Evidence Based
11

Phenylalanine: Potential Benefits + Foods & Side Effects

Written by Aleksa Ristic, MS (Pharmacy) | Reviewed by Ana Aleksic, MSc (Pharmacy), Nattha Wannissorn, PhD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Aleksa Ristic, MS (Pharmacy) | Reviewed by Ana Aleksic, MSc (Pharmacy), Nattha Wannissorn, PhD | Last updated:

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Found in many foods, this amino acid builds important neurotransmitters and proteins. Phenylalanine has potential health benefits for the skin and brain, but some people should avoid it by all means. Read on to find out if it’s right for you.

What is Phenylalanine?

Phenylalanine is an amino acid that builds proteins, neurotransmitters, and other crucial molecules in your body. The body can’t produce phenylalanine, which makes it an essential amino acid we need to get from food [1, 2].

Nutritional supplements can contain different forms of phenylalanine with unique mechanisms and health effects – we’ll dive into details about each one.

Structure

Source: https://commons.wikimedia.org/wiki/File:Phenylalanin(L-und_D-Phenylalanin)_V1.png

Phenylalanine molecule has 2 different forms, L- and D-phenylalanine, which are “mirror images” with the same structure. As you can see in the image above, they are only differently oriented in space [3].

L-phenylalanine is the active form that occurs naturally in a variety of foods. Your body uses it to make proteins and other molecules [4, 5].

D-phenylalanine is the synthetic form made in the lab. Your body partly converts it to the L-form or eliminates it via urine, but it also has some specific health effects discussed below [6, 7].

Supplements can contain either form or a mixture of their equal amounts, known as DLPA (DL-phenylalanine).

Snapshot

Proponents:

  • Helps with vitiligo
  • May help with depression
  • Supports fat burning
  • May reduce substance dependence

Skeptics:

  • May cause nausea
  • Dangerous for people with phenylketonuria
  • Has mixed effects on blood pressure
  • Interacts with Parkinson’s disease treatment

Phenylalanine Foods

Most protein-rich foods contain decent amounts of L-phenylalanine. These include [8, 9]:

  • Eggs
  • Milk and dairy products
  • Legumes (beans and peanuts)
  • Sunflower and sesame seeds
  • Red meat and poultry
  • Fish

Eating a variety of good protein sources will grant you an optimal phenylalanine intake.

People with an inborn metabolic disorder called phenylketonuria (PKU) should avoid all foods and supplements high in phenylalanine (more details in the “Side Effects and Precautions” section) [10].

Health Benefits

How It Works

Source: N.V. Bhagavan, Chung-Eun Ha, in Essentials of Medical Biochemistry, 2011

Joined with other amino acids, L-phenylalanine builds proteins that support the structure and delicate functions of the entire body.

L-phenylalanine converts to another amino acid, tyrosine, which further gives [11, 12]:

It also boosts the release of CCK, a hormone that reduces appetite [13].

Thanks to these complex roles, L-phenylalanine may impact mental health, cognition, skin appearance, weight control, and more.

The body can’t use the other, D form of this amino acid as a building block. Instead, D-phenylalanine combats inflammation and increases natural opioids, which control pleasure, pain, immunity, and mood [14, 15].

Possibly Effective:

1) Vitiligo

Vitiligo is an autoimmune disease in which cells that make the skin pigment melanin gets destroyed. As a result, melanin content drops and parts of the skin lose color [16].

L-phenylalanine converts into melanin and acts as a natural remedy for vitiligo [17].

In a study of 70 vitiligo patients, a combination of topical (10% gel) and oral (100 mg/kg daily) L-phenylalanine showed promising results. It recovered skin color in 90% of the patients when added to standard treatment with UV light and medications [18].

Other trials with over 270 vitiligo patients confirmed the beneficial effects of phenylalanine creams and supplements in combination with UV therapy [19, 20, 21].

2) Depression

L-phenylalanine enables the production of mood-boosting neurotransmitters such as dopamine and norepinephrine. Low brain levels of these chemicals often lurk behind the symptoms of depression [11, 22].

A diet devoid of phenylalanine, tyrosine, and tryptophan may impair mood and increase irritability. According to a review of clinical data, these amino acids may help with mild to moderate depression [23, 24].

In one clinical trial with 155 depressed patients, a combination of L-phenylalanine (250 mg daily) and standard treatment was beneficial in 80-90% of the cases [25].

Blood and urine levels of phenylalanine tend to be lower in depressed patients than in healthy people. Supplementation with L-phenylalanine improved mood in 31/40 such patients [26].

A supplement with both forms, DL-phenylalanine (DLPA), has also shown positive results in depression. DLPA (150-200 mg daily) had the same effect as an antidepressant, imipramine, in a study of 40 depressed people [27, 28].

In two more clinical trials, it removed the symptoms of depression in 29/43 patients and provided moderate improvement in 4 cases [29, 30].

However, most of the above studies are over 40 years old and lack placebo controls.

D-phenylalanine alone provided no benefits in 11 depressed patients. It even worsened the condition in 2 cases [31].

Low-quality clinical evidence suggests that L-phenylalanine and DLPA may help with mild-to-moderate depression. Further research is warranted.

Insufficient Evidence:

No valid clinical evidence supports the use of phenylalanine supplements for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.

3) Weight and Appetite Control

Many supplements are promoted to stimulate weight loss, but none of them has yet been supported by strong clinical evidence and approved by the health authorities. A healthy, calorie-controlled diet and increased physical activity remain the only proven strategies for weight control [32].

In two studies of 52 women, mega doses of L-phenylalanine (10 g) reduced food intake by 11-15%. The effects depended on dietary habits and the phase of the menstrual cycle. Women might respond better to appetite suppressants in the first half of the menstrual cycle (follicular phase), but more research is needed [13, 33, 34, 35].

In over 300 obese adults, supplements with L-phenylalanine significantly reduced belly fat when combined with exercise and dieting, but they didn’t cause weight loss [36, 37].

Other ingredients in these supplements – such as arginine, chromium, and inulin – have likely contributed to the results.

Pre-exercise supplementation with 3 g of L-phenylalanine enhanced fat burning in six volunteers. A mixture containing this amino acid showed the same results in 10 people [38, 39].

According to limited clinical evidence, L-phenylalanine can reduce appetite and stimulate fat burning, but it doesn’t seem to support weight loss.

4) Substance Dependence

Our internal opioids don’t just block pain signals, they regulate a deep-seated reward system in our brain that makes certain things enjoyable [40].

D-phenylalanine may increase our internal opioids. This effect could be of use in people who have suppressed internal opioids due to substance dependence and withdrawal [14, 41].

In a study on 20 patients struggling with alcohol withdrawal, a supplement with D-phenylalanine, 5-HTP, and glutamine greatly reduced their psychiatric symptoms and stress [42].

The effect was likely due to increased brain levels of dopamine and enkephalins.

A group of scientists observed the ability of D-phenylalanine and hydrocinnamic acid to reduce alcohol addiction in mice by recovering internal opioids [43].

Recent research has hypothesized that D-phenylalanine (DPA) and N-acetylcysteine (NAC) may work in synergy to relieve addictions. NAC balances glutamate in the reward system and counteracts DPA’s dopamine stimulation. As a result, dopamine levels stay in the optimal range [44].

Clinical trials are yet to confirm the safety and efficacy of this combination.

5) Parkinson’s Disease

As mentioned, L-phenylalanine is a precursor for dopamine, a vital neurotransmitter that’s deficient in Parkinson’s disease. This fact has inspired some research in the past, but the potential benefits of phenylalanine for this indication are still in the domain of theory [45].

Phenylalanine can even interact with a drug for Parkinson’s disease and thus cause variations in treatment response (more details in “Drug Interactions” below).

Possibly Ineffective:

Pain Management

D-phenylalanine boosts natural opioids – beta-endorphins and enkephalins – which play a central role in pain management. Some doctors have been using it as an add-on supplement for different types of chronic pain since the ‘80s, sometimes in combination with acupuncture [46].

However, clinical trials are less encouraging.

In one study of 56 patients who underwent a tooth extraction, D-phenylalanine supplementation (4 g) increased the effects of acupuncture anesthesia by 35%. It provided a 26% improvement in another study of 30 patients with lower back pain, but the authors found it non-significant [47].

It offered no significant benefits to 30 people with chronic pain. A study on monkeys also found a weak effect on pain [48, 49].

Studies on rats and mice suggest mild pain-killing effects of D-phenylalanine, alone and in combination with other drugs [50, 51].

Some doctors reported success with phenylalanine as a complementary approach to pain management, but available clinical evidence doesn’t support this.

Attention Disorders

L-phenylalanine helps in the formation of dopamine, which plays a vital role in mental health and attention. Low dopamine levels may trigger ADHD symptoms [52].

DLPA supplement (1200 mg daily for 2 weeks) improved the symptoms such as anger, restlessness, and poor concentration in 19 adults with ADD. However, three months after the study, the beneficial effects disappeared [53].

A review of clinical trials found no significant benefits of phenylalanine for ADHD [54].

Phenylalanine doesn’t seem to be effective for attention disorders.

Phenylalanine Side Effects & Safety

All supplement forms were safe in clinical trials and didn’t cause significant side effects. However, L-phenylalanine did cause nausea in higher doses [13, 18, 55, 30, 29].

According to the FDA, L-phenylalanine is “generally recognized as safe” (GRAS) in foods and supplements [56].

Diabetes Risk

In 1680 young adults, increased intake of aromatic and branched-chain amino acids was associated with insulin resistance and a higher risk of diabetes. The connection was stronger in men and included [57]:

Effects on Blood Pressure

There is public concern about the potential of phenylalanine to raise blood pressure, but studies reveal mixed effects.

An observational trial with over 4,000 patients showed a connection between increased intake of phenylalanine and high blood pressure. However, no controlled clinical trials have confirmed this effect. [58].

On the other hand, phenylalanine reduced blood pressure and protected blood vessels in multiple studies on rats [59, 60, 61, 62].

Additional studies should cast more lights on these contradicting findings.

Phenylketonuria

People with a rare inborn metabolic disorder – phenylketonuria (PKU) – are unable to break down phenylalanine properly. The buildup of this amino acid, in turn, causes brain damage and cognitive impairment [63, 64, 65].

The disorder occurs due to an inherited lack of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine to tyrosine. PAH deficiency is a milder form in which patients can metabolize small amounts of phenylalanine [66].

Phenylketonurics should follow a special low-protein diet to minimize the intake of phenylalanine. Obviously, they should steer clear of all phenylalanine supplements [67, 68].

Aspartame is an artificial sweetener that contains phenylalanine. Sugar-free items such as diet soda (and chewing gum) may contain it.

All foods and drinks with added phenylalanine or aspartame must have a warning label for people with phenylketonuria.

Besides the strict dietary regimen, scientists are developing new treatment options for this disorder, including gene therapy [69].

Drug Interactions

Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let him know about all drugs and supplements you are using or considering.

Phenylalanine interacts with L-DOPA, a drug for Parkinson’s disease. It hinders the transport of L-DOPA to the brain, which may cause sharp changes in a clinical response known as the “on-off” phenomenon [70]

The fact that some people use phenylalanine supplements for Parkinson’s disease makes this interaction particularly important and dangerous.

Sensitive Groups

Children seem to tolerate phenylalanine well, but they should take it under medical supervision. Pregnant women should avoid all phenylalanine supplements until we know more about their safety. Mothers with phenylketonuria (PKU) should avoid phenylalanine supplements by all means [54, 55].

Phenylalanine Supplements & Reviews

Phenylalanine supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.

The opinions expressed in this section are solely from the users who may or may not have a medical background. SelfHacked does not endorse any specific product, service, or treatment. Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice because of something you have read on SelfHacked.

Both L- and D-phenylalanine usually come in 500 mg pills. Bulk powder with L-phenylalanine is also available.

Users report positive experiences with L-phenylalanine for depression, anxiety, and mental clarity. However, many people had no benefits from this supplement, and some even experienced mood swings and headaches.

People take D-phenylalanine for chronic pain, and most of them are satisfied with the results. Others mention it improved their focus and energy.

For DL-phenylalanine supplements and user reviews, check out our DLPA article.

Phenylalanine Genetics

Variants in the gene that codes for phenylalanine hydroxylase (PAH) are associated with phenylketonuria. In a clinical trial with 160 subjects, the SNPs EX6-96 and R243Q were the most common PAH variants among phenylketonurics [71].

Other common variants in this gene have been linked to memory performance in healthy people. In a study on 600 adults, those with the ”GG” genotype on rs2037639 had worse verbal memory [72].

Takeaway

Phenylalanine builds neurotransmitters and proteins that support mental health and metabolism. Protein-rich foods such as eggs, cheese, beans, and meat are excellent sources of this amino acid.

Phenylalanine may help with vitiligo and improve depression treatment. There’s insufficient evidence for weight control, substance dependence, and Parkinson’s disease. It probably won’t work for pain management and attention disorders.

Supplements are likely safe for healthy adults. Pregnant women, children, and people taking drugs for Parkinson’s disease should avoid them. People with phenylketonuria can’t metabolize phenylalanine. They should avoid all sources of this amino acid and follow a special low-protein diet. Make sure to consult your doctor before supplementing.

About the Author

Aleksa Ristic

Aleksa Ristic

MS (Pharmacy)
Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets. 
Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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